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On November 12, 2024, the National Prevention Science Coalition to Improve Lives hosted the second of two briefings on best strategies for allocating the pharmaceutical settlement dollars to abate the opioid crisis. The substance use crises continue to rage—there are still thousands of deaths, many more with substance use disorders, and teenagers on the path to risky drug taking and addiction. Public health experts and agencies are working to inform the public and eliminate fentanyl and other harmful substances from the drug supply. However, misuse of addictive substances and their devastating and costly consequences will not disappear unless we implement a comprehensive, proactive, and sustained approach to substance use and addiction. There is now an unprecedented opportunity to do this right by smartly allocating the National Prescription Opiate Litigation. The substantial body of scientific knowledge and best practices generated to date offer workable solutions. Investments in prevention strategies are cost-effective, reducing levels of systems involvement and need for substance use treatment, and forestalling the enormous financial, productivity, health, and social costs of untreated addiction. As Americans grow increasingly attuned to the substance use crisis the country is facing, let’s use the mounds of evidence that have been accumulated to make smart decisions and ensure that settlement funds are being heavily invested in prevention and children’s health and well-being, and not just plugging up holes in the addiction-crisis dam. The first briefing featured experts in risk factors that influence pathways to substance use and addiction, authors of key recommendations for spending the settlement funds, and public health solutions that hold promise to turn this crisis around by investing in a full spectrum of responses to the crisis, rather than singularly focused approaches (e.g., only interdiction, prescription regulations, or treatment). Part II of this briefing series provided additional guidance in greater detail for policymakers, agency officials, and community stakeholders.